Association Between Seroclearance of Hepatitis B Surface Antigen and Long-term Clinical Outcomes of Patients With Chronic Hepatitis B Virus Infection: Systematic Review and Meta-analysis

Ryan T Anderson; Hannah S J Choi; Oliver Lenz; Marion G Peters; Harry L A Janssen; Poonam Mishra; Eric Donaldson; Gabriel Westman; Stephanie Buchholz; Veronica Miller; Bettina E Hansen

doi:10.1016/j.cgh.2020.05.041

Association Between Seroclearance of Hepatitis B Surface Antigen and Long-term Clinical Outcomes of Patients With Chronic Hepatitis B Virus Infection: Systematic Review and Meta-analysis

Clin Gastroenterol Hepatol. 2021 Mar;19(3):463-472. doi: 10.1016/j.cgh.2020.05.041. Epub 2020 May 27.

Authors

Affiliations

¹ The Forum for Collaborative Research, University of California, Berkeley, California, School of Public Health, Washington, District of Columbia.
² Toronto Centre for Liver Disease, University Health Network, Toronto, Ontario, Canada.
³ Janssen Research and Development, Antwerp, Belgium.
⁴ AIDS Clinical Trial Group, Chicago Illinois.
⁵ Division of Safety.
⁶ Division of Virology, US Food and Drug Administration, Silver Spring, Maryland.
⁷ Swedish Medical Products Agency, Uppsala, Sweden; Department of Medical Sciences, Section of Infectious Diseases, Uppsala University, Uppsala, Sweden.
⁸ Federal Institute for Drugs and Medical Devices, Bonn, Germany.
⁹ Department of Biostatistics, Institute of Health Policy, Management and Evaluation, University of Toronto, Toronto, Ontario, Canada. Electronic address: Bettina.Hansen@utoronto.ca.

PMID: 32473348
DOI: 10.1016/j.cgh.2020.05.041

Abstract

Background & aims: Seroclearance of hepatitis B surface antigen (HBsAg) is the desired end point of treatment for chronic hepatitis B virus (HBV) infection, according to guidelines. We performed a systematic review and meta-analysis to evaluate the strength of the association between HBsAg seroclearance and long-term clinical outcomes.

Methods: We performed a systematic review of the PubMed, EMBASE, and Cochrane Library databases for articles that assessed HBsAg status and reported the incidence of hepatocellular carcinoma (HCC), liver decompensation, liver transplantation, and/or all-cause mortality during follow-up evaluation. We performed a meta-analysis of rate ratios (RR) using a random-effects model independently for each end point and for a composite end point.

Results: We analyzed data from 28 studies, comprising a total of 188,316 patients with chronic HBV infection (treated and untreated), and 1,486,081 person-years (PY) of follow-up evaluation; 26 reported data on HCC, 7 on liver decompensation, and 13 on liver transplantation and/or death. The composite event rates were 0.19/1000 PY for the HBsAg seroclearance group and 2.45/1000 PY for the HBsAg-persistent group. Pooled RRs for the HBsAg seroclearance group were 0.28 for liver decompensation (95% CI, 0.13-0.59; P = .001), 0.30 for HCC (95% CI, 0.20-0.44; P < .001), 0.22 for liver transplantation and/or death (95% CI, 0.13-0.39; P < .001), and 0.31 for the composite end point (95% CI, 0.23-0.43; P < .001). No differences in RR estimates were observed among subgroups of different study or patient characteristics.

Conclusions: In a systematic review and meta-analysis, we found seroclearance of HBsAg to be associated significantly with improved patient outcomes. The results are consistent among different types of studies, in all patient subpopulations examined, and support the use of HBsAg seroclearance as a primary end point of trials of patients with chronic HBV infection.

Keywords: Biomarker; Prognostic Factor; Surrogate Endpoint; Viral Hepatitis.

Publication types

Meta-Analysis
Systematic Review

MeSH terms

Carcinoma, Hepatocellular* / epidemiology
DNA, Viral
Hepatitis B Surface Antigens
Hepatitis B e Antigens
Hepatitis B virus / genetics
Hepatitis B*
Hepatitis B, Chronic* / epidemiology
Humans
Liver Neoplasms*

Substances

DNA, Viral
Hepatitis B Surface Antigens
Hepatitis B e Antigens